POS1215 IMMUNE CORRELATES AND CLINICAL COURSE OF PATIENTS WITH RHEUMATOID ARTHRITIS FOLLOWING VACCINATION WITH ANTI SARS-CoV-2 mRNA BASED VACCINES: RESULTS FROM A PROSPECTIVE, OBSERVATIONAL AND CONTROLLED STUDY
Authors: K. Schmiedeberg, I. A. Abela, N. B. Pikor, N. Vuilleumier, M. Schwarzmueller, S. Epp, S. Pagano, S. Grabherr, A. B. Patterson, M. Nussberger, A. Trkola, B. Ludewig, J. Von Kempis, A. Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2022)

Background Vaccines are highly effective in preventing COVID-19 associated hospitalization and deaths. Strong and persistent immune responses are critical to provide protection for patients with immunomodulatory therapies. Objectives To assess humoral and cellular immune responses following 2 doses of an anti-SARS-CoV-2 mRNA based vaccine in rheumatoid arthritis (RA). Immune responses in patients treated with csDMARDs, bDMARDs (with the exception of rituximab) and JAK inhibitors were compared to healthy controls (HC) over 24 weeks. In addition, disease activity by CDAI and vaccine-induced side effects were prospectively monitored. Methods The RECOVER trial ( R heumatoid C ovid-19 V accin e Immune R esponse) is a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 HC. Clinical assessment and blood sampling was performed at baseline, 3 weeks after the 1 st and 2 weeks after the 2 nd vaccine dose and at week 12 and 24 after the 1 st . Antibody response to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The seroprofiling assay ABCORA, which has been suggested as a surrogate for neutralization, 1 was used to determine IgG, IgA and IgM responses to RBD, S1, S2 and N. The neutralizing activity NT50 at week 12 was assessed against Wuhan-Hu-1 pseudoviruses (HIV-based). IFN-y ELISpots were applied to detect spike-reactive T cell responses after in vitro stimulation with a spike peptide mix. Results Baseline characteristics of participants are detailed in Table 1. Vaccination was well tolerated with no differences between RA patients and HC. At baseline, the majority of RA patients were in remission/LDA (57/77, 74%), this proportion decreased to 51% (39/77) after the second vaccine dose (p = 0.005). Treatment adjustments were required in 11/77 patients. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein). In contrast to HC, anti-S titers were lower at all timepoints with significantly reduced titers observed in patients on abatacept and JAK inhibitors (Figure 1). Potent neutralizing activity (NT50 ≥ 250)) was detected in all HC at week 12, in contrast to 62% RA patients. NT50 correlated to the results based on the ABCORA assay. Peak anti-S titers (2 weeks after 2 nd vaccine) were predictive of NT50 ≥ 250 at week 12 (p &lt; 0.0001). In contrast to marked differences in the humoral immune responses, spike-protein specific IFN-α secreting T cells were largely unaltered by different DMARD regimen. Table 1. Baseline characteristics RA patients (n = 77) HC (n = 21) p-value Age (yrs), mean (± SD) 64 (13) 44 (14) &lt; 0.0001 Female, n (%) 46 (60) 15 (71) NS Vaccination type mRNA-1273, n (%) 12 (16) 0 (0) 0.06 BNT162b2, n (%) 65 (84) 21 (100) Disease activity (CDAI ) Remission (≤ 2.8), n (%) 17/77 (22) Low (2.9 - 10), n (%) 40/77 (52) Moderate (10.1 - 22.0), n (%) 15/77 (20) High (22.1 - 76.0), n (%) 5/77 (7) DMARD therapy Mono csDMARDs, n (%) 22/77 (29) bDMARDs, n (%) 35/77 (46) Mono bDMARDs, n (%) 14/35 (40) JAKi, n (%) 20/77 (26) Mono JAKi, n (%) 8/20 (40) Prednisone, n (%) 25/77 (33) Mean daily dose (mg ± SD) 5.6 ± 3.6 Conclusion RA patients, in comparison with HC, revealed a slower kinetic and lower magnitude of humoral immune responses depending on the treatment regimen while T cell responses were largely maintained. Peak anti-S responses two weeks after the second vaccine were able to predict the development of potent neutralizing activity and should therefore be considered to individually tailor vaccination strategies. References [1]Abela I et al. Nature Commun 2021. doi.org/10.1038/s41467-021-27040-x Disclosure of Interests Kristin Schmiedeberg: None declared, Irene A. Abela: None declared, Natalia Barbara Pikor: None declared, Nicolas Vuilleumier: None declared, Magdalena Schwarzmueller: None declared, Selina Epp: None declared, Sabrina Pagano: None declared, Sarah Grabherr: None declared, Angelica Brooke Patterson: None declared, Madalina Nussberger: None declared, Alexandra Trkola: None declared, Burkhard Ludewig: None declared, Johannes von Kempis: None declared, Andrea Rubbert-Roth Speakers bureau: Abbvie, Pfizer, Sanofi, UCB, BMS, Lilly, Gilead, Roche, Consultant of: Abbvie, Gilead, Lilly, BMS, Sanofi